This project will assess the capacity of cerebral neocortex to exhibit synaptic modifiability in response to repeated stimulation of input fibers, and seeks furthermore to characterize the specific nature and properties of this modifiability. These aims will be achieved through electrophysiological stimulation and recording studies from cortical tissue slices maintained in vitro, and perfused with cerebrospinal fluid and pharmacologically active substances. Use-dependent alteration of synaptic function could be manifested as enhancement (long-term potentiation; LTP) or suppression (long-term depression; LTD). Studies that can determine the true direction of such processes in cortex can be conducted in vitro in slices of excised tissue, at both intracellular and extracellular eve s. In broad terms, the objective of the proposed research overall is the goal of more accurately understanding the cellular mechanisms involved in the establishment of long-term plasticity of synaptic transmission in mammalian visual cortex. The 3 specific objectives concern: 1) to determine the optimal stimulus parameters in vitro for elicitation of cortical LTP, and to assess whether parameters different from those cause LTD to appear. 2) To explore whether apparent LTD as judged extracellularly, represents a form of "masked" LTP, as seen intracellularly using manual step-clamping of membrane voltage. 3) To evaluate the contributions of amino acid receptors to the different components of stimulus-induced field potentials at low and high frequencies, to gain new information about synaptic processes responsible for normal information processing and use-dependent modification of responses. These goals are relevant to all types of neurological disorders in which loss of input results in a modification, or redistribution of neural connections in brain. Most significant in the present context, would be cortical abnormalities resulting from visual disorders such as amblyopia, or in aging processes where cholinergic inputs to cortex degenerate, such as in Alzheimer's, recovery from stroke where regional ischemia occurs, or in senile dementia.